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The basic tribological experiments have reported that nano-graphene lubricating oil has excellent anti-friction and anti-wear properties, which has been widely concerned. However, the real anti-friction effect of nano-graphene lubricating oil and its impact on engine power performance, economic performance and emission performance remain to be proved. This has seriously hindered the popularization and application of nano-graphene lubricating oil in the engine field. In this paper, nano-graphene powder was chemically grafted to prepare nano-graphene lubricating oil with high dispersion stability. The influence of nano-graphene on physicochemical properties of lubricating oil was studied, and the influence of nano-graphene on engine power performance, economic performance and emission performance was explored. The results show that after modification, the dispersion of nano-graphene in lubricating oil is improved. Compared with pure lubricating oil, the addition of nano-graphene makes the kinematic viscosity of lubricating oil slightly lower, and has little effect on the density, flash point, pour point and total acid value of lubricating oil. The reversed towing torque of nano-graphene lubricating oil is reduced by 1.82-5.53%, indicating that the friction loss decreases. The specific fuel consumption of the engine is reduced, which indicates that the fuel economic performance is improved. Engine HC+NOX, CH4, CO2 emissions do not change much, but particulate matter (PM) emissions increase by 8.85%. The quantity concentration of nuclear particles, accumulated particles and total particles of nano-graphene lubricating oil are significantly higher than that of pure lubricating oil. And the increase of the quantity concentration of accumulated particles is more obvious than that of nuclear particles, and the larger the load, the more obvious this phenomenon. In order to apply nano-graphene lubricating oil to the engine, it is also necessary to further study its impact on the post-processing system, adjust the control strategy of the post-processing system and then test and calibrate.
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Grafite , Lubrificantes , Viscosidade , Grafite/química , Lubrificantes/química , Gasolina/análise , Nanoestruturas/química , Óleos/química , Lubrificação , Emissões de Veículos/análiseRESUMO
The efficacy and safety of mRNA vaccines both rely on a fine-tuning of specific humoral and cellular immune responses. Instead of adjustments in vaccine component, we proposed a concept of chronological management of adjuvant effect to modulate the adaptive immune potency and preference inspired by natural virus infection. By simulating type I interferon expression dynamics during viral infection, three vaccine strategies employing distinct exposure sequences of adjuvant and mRNA have been developed, namely Precede, Coincide, and Follow. Follow, the strategy of adjuvant administration following mRNA, effectively suppressed tumor progression, which was attributed to enhanced mRNA translation, augmented p-MHC I expression, and elevated CD8+ T cell response. Meanwhile, Follow exhibited improved biosafety, characterized by reduced incidences of cardiac and liver toxicity, owing to its alteration to the vaccination microenvironment between successive injections. Our strategy highlights the importance of fine-tuning adjuvant effect dynamics in optimizing mRNA vaccines for clinical application.
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INTRODUCTION: Insulin resistance (IR) is associated with multiple pathological features. Although p53- or TRIB3-orchestrated IR is extensively studied in adipose tissue and liver, the role of p53-TRIB3 axis in myocardial IR remains unknown, and more importantly target-directed therapies of myocardial IR are missing. OBJECTIVES: Considering the beneficial effects of sulforaphane (SFN) on cardiovascular health, it is of particular interest to explore whether SFN protects against myocardial IR with a focus on the regulatory role of p53-TRIB3 axis. METHODS: Mouse models including cardiac specific p53-overexpressing transgenic (p53-cTg) mice and Trib3 knockout (Trib3-KO) mice, combined with primary cardiomyocytes treated with p53 activator (nutlin-3a) and inhibitor (pifithrin-α, PFT-α), or transfected with p53-shRNA and Trib3-shRNA, followed by multiple molecular biological methodologies, were used to investigate the role of p53-TRIB3 axis in SFN actions on myocardial IR. RESULTS: Here, we report that knockdown of p53 rescued cardiac insulin-stimulated AKT phosphorylation, while up-regulation of p53 by nutlin-3a or p53-cTg mice blunted insulin sensitivity in cardiomyocytes under diabetic conditions. Diabetic attenuation of AKT-mediated cardiac insulin signaling was markedly reversed by SFN in p53-Tgfl/fl mice, but not in p53-cTg mice. Importantly, we identified TRIB3 was elevated in p53-cTg diabetic mice, and confirmed the physical interaction between p53 and TRIB3. Trib3-KO diabetic mice displayed improved insulin sensitivity in the heart. More specifically, the AMPKα-triggered CHOP phosphorylation and degradation were essential for p53 on the transcriptional regulation of Trib3. CONCLUSION: Overall, these results indicate that inhibiting the p53-TRIB3 pathway by SFN plays an unsuspected key role in the improvement of myocardial IR, which may be a promising strategy for attenuating diabetic cardiomyopathy (DCM) in diabetic patients.
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Electrohydrodynamic (EHD) direct-writing has recently gained attention as a highly promising additive manufacturing strategy for fabricating intricate micro/nanoscale architectures. This technique is particularly well-suited for mimicking the extracellular matrix (ECM) present in biological tissue, which serves a vital function in facilitating cell colonization, migration, and growth. The integration of EHD direct-writing with other techniques has been employed to enhance the biological performance of scaffolds, and significant advancements have been made in the development of tailored scaffold architectures and constituents to meet the specific requirements of various biomedical applications. Here, a comprehensive overview of EHD direct-writing is provided, including its underlying principles, demonstrated materials systems, and biomedical applications. A brief chronology of EHD direct-writing is provided, along with an examination of the observed phenomena that occur during the printing process. The impact of biomaterial selection and architectural topographic cues on biological performance is also highlighted. Finally, the major limitations associated with EHD direct-writing are discussed.
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Colangiocarcinoma , Granuloma de Células Plasmáticas , Humanos , Pessoa de Meia-Idade , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Diagnóstico Diferencial , Granuloma de Células Plasmáticas/diagnóstico , Granuloma de Células Plasmáticas/diagnóstico por imagem , Hepatopatias/diagnóstico , FemininoRESUMO
Acute lung injury (ALI) is associated with the leukocyte infiltration and inflammation. Previous studies have shown that miR-146a is a valid regulator of the macrophage polarization in vitro inflammatory model. However, it is unclear whether miR-146a plays a protective role in ALI via modulating macrophage inflammation. To explore the potential therapeutic effect mechanism of miR-146a on ALI. We analyzed the expression of miR-146a in acute injured lung tissues and differentiated macrophage. Lipopolysaccharide (LPS) and interleukin-4 (IL-4) were employed in provoking the macrophage to polarization. We used miR-146a mimics to improve the overexpression of miR-146a and investigated the effect of increased miR-146a on LPS-induced ALI mice via the target of macrophage polarization. We showed that the expression of miR-146a markedly decreased in injured lung tissue and type M1 macrophage, while increased miR-146a expression exhibited in type M2 macrophage. Moreover, overexpression of miR-146a in LPS-induced macrophage reversed inflammatory M1 phenotype to anti-inflammatory M2 phenotype and mitigated inflammatory level via inhibiting Notch 1 signaling pathway. Hence, inflammation, infiltration, integrity of capillary barrier, and histology in ALI model were corrected after miR-146a overexpression treatment. These results suggested that miR-146a promotes type M2 macrophage polarization via restraining Notch 1 signaling pathway. Overexpression of miR-146a prevents inflammation damage and ameliorates lung damage after LPS induction. Therefore, miR-146a may serve as a promising target for the therapy of ALI in the future.
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Lesão Pulmonar Aguda , MicroRNAs , Receptor Notch1 , Transdução de Sinais , Animais , Camundongos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/metabolismo , MicroRNAs/metabolismo , Receptor Notch1/metabolismoRESUMO
BACKGROUND: Surgical site infection (SSI) is one of the most common complications after gastric cancer (GC) surgery. The occurrence of SSI can lead to a prolonged postoperative hospital stay and increased medical expenses, and it can also affect postoperative rehabilitation and the quality of life of patients. Subcutaneous fat thickness (SFT) and abdominal depth (AD) can be used as predictors of SSI in patients undergoing radical resection of GC. AIM: To explore the potential relationship between SFT or AD and SSI in patients undergoing elective radical resection of GC. METHODS: Demographic, clinical, and pre- and intraoperative information of 355 patients who had undergone elective radical resection of GC were retrospectively collected from hospital electronic medical records. Univariate analysis was performed to screen out the significant parameters, which were subsequently analyzed using binary logistic regression and receiver-operating characteristic curve analysis. RESULTS: The prevalence of SSI was 11.27% (40/355). Multivariate analyses revealed that SFT [odds ratio (OR) = 1.150; 95% confidence interval (95%CI): 1.090-1.214; P < 0.001], AD (OR = 1.024; 95%CI: 1.009-1.040; P = 0.002), laparoscopic-assisted surgery (OR = 0.286; 95%CI: 0.030-0.797; P = 0.017), and operation time (OR = 1.008; 95%CI: 1.001-1.015; P = 0.030) were independently associated with the incidence of SSI after elective radical resection of GC. In addition, the product of SFT and AD was a better potential predictor of SSI in these patients than either SFT or AD alone. CONCLUSION: SFT and AD are independent risk factors and can be used as predictors of SSI in patients undergoing radical resection of GC.
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Heavy metals from slag waste (HMSWs) have attracted much attention because of their serious toxicity to the environment and human organs, especially hepatotoxicity. The aim of this study was to explore the effects of different HMSWs exposure on mitochondrial lipid peroxidation, microsomal drug metabolizing enzyme activities as well as their relationship in the rat liver injury. Based on toxicogenomic analysis, heavy metals including iron, copper, cobalt, nickel and manganese, might interfere with pathophysiological processes such as oxidative stress, cell death, and energy metabolism regulation in vivo, and participate in the regulation of HIF-1 signaling pathway, peroxisomes, drug metabolism-cytochrome P450, ferroptosis, and other signaling pathways. HMSWs exposure caused weight loss, and significantly increased lactate dehydrogenase (LDH), malondialdehyde (MDA), alanine transaminase (ALT), and aspartate transaminase (AST) in different groups of rat liver, suggesting the presence of mitochondrial lipid peroxidation damage. In addition, the ratios of AST/ALT and ALT/LDH were down-regulated, especially the ALT/LDH ratios were less than 1, indicating that hepatic ischemic injury occurred in the process of liver injury. The superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) activities in rats also showed significant decreases, indicating the occurrence of hepatic oxidative/antioxidant dysfunction imbalance. Further decision tree analysis of live biochemical abnormalities suggested that AST > 58.78 U/gprot and MDA > 173.2 nmol/mgprot could be used for hepatotoxicity warning. Liver microsomal cytochrome P4501A2 (CYP1A2) and 3A1 (CYP3A1) enzymes were also involved in the hepatotoxic process of heavy metals. These results suggest that lipid peroxidation damage and metabolic damage in liver mitochondria and peroxisomes, may be one of the key events in heavy metal-induced liver injury.
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Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas , Ratos , Humanos , Animais , Peroxidação de Lipídeos , Antioxidantes/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Alanina Transaminase/metabolismo , Aspartato Aminotransferases/metabolismo , Aspartato Aminotransferases/farmacologia , Ferro/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismoRESUMO
Evidence from experimental and clinical studies implicates immuno-inflammatory responses as playing an important role in epilepsy-induced brain injury. Captopril, an angiotensin-converting enzyme inhibitor (ACEi), has previously been shown to suppress immuno-inflammatory responses in a variety of neurological diseases. However, the therapeutic potential of captopril on epilepsy remains unclear. In the present study, Sprague Dawley (SD) rats were intraperitoneally subjected to kainic acid (KA) to establish a status epilepticus. Captopril (50 mg/kg, i.p.) was administered daily following the KA administration from day 3 to 49. We found that captopril efficiently suppressed the KA-induced epilepsy, as measured by electroencephalography. Moreover, captopril ameliorated the epilepsy-induced cognitive deficits, with improved performance in the Morris water maze, Y-maze and novel objective test. RNA sequencing (RNA-seq) analysis indicated that captopril reversed a wide range of epilepsy-related biological processes, particularly the glial activation, complement system-mediated phagocytosis and the production of inflammatory factors. Interestingly, captopril suppressed the epilepsy-induced activation and abnormal contact between astrocytes and microglia. Immunohistochemical experiments demonstrated that captopril attenuated microglia-dependent synaptic remodeling presumably through C3-C3ar-mediated phagocytosis in the hippocampus. Finally, the above effects of captopril were partially blocked by an intranasal application of recombinant C3a (1.3 µg/kg/day). Our findings demonstrated that captopril reduced the occurrence of epilepsy and cognitive impairment by attenuation of inflammation and C3-mediated synaptic phagocytosis. This approach can easily be adapted to long-term efficacy and safety in clinical practice.
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Disfunção Cognitiva , Epilepsia , Animais , Captopril/farmacologia , Captopril/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Inflamação/tratamento farmacológico , Ácido Caínico/toxicidade , Fagocitose , Ratos , Ratos Sprague-DawleyRESUMO
A novel in vitro 3D micronucleus assay was developed in China using the EpiSkin™ 3D human skin model. This EpiSkin™ Micronucleus Assay showed good predictivity and reproducibility during internal validation and is expected to contribute to in vitro genotoxicity testing as a follow-up for positive results from 2D micronucleus assay. Having developed the assay in one laboratory, further work focused on the transferability and inter-laboratory reproducibility in two additional Chinese authority laboratories (Guangdong Provincial Center for Disease Control and Prevention and Zhejiang Institute for Food and Drug Control). Formal training was provided for both laboratories, which resulted in good transferability based on the results of two positive compounds, such as mitomycin C and vinblastine. Independent experiments were then performed, and inter-laboratory reproducibility was checked using 2-acetylaminofluorene, 5-fluorouracil, 2,4-dichlorophenol, and d-limonene. The dose-responses of the positive control chemical, mitomycin C, were similar to those of the developing laboratory, and all test chemicals were correctly classified by all laboratories. Overall, there was a good transferability as well as intra- and inter-laboratory reproducibility of the EpiSkin™ Micronucleus Assay. This study further confirmed the assay's robustness and provided confidence to enter following validation stages for scientific acceptance.
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Mitomicina , Vimblastina , Humanos , Testes para Micronúcleos/métodos , Reprodutibilidade dos Testes , Mitomicina/toxicidade , Limoneno , 2-Acetilaminofluoreno , FluoruracilaRESUMO
Facial artery pseudoaneurysms are rare and mostly a result of blunt injury. Since the facial arteries are well protected by facial soft tissue and the lumen of the facial artery is thin and small in diameter, a sharp injury usually leads to complete transection rather than partial laceration of the blood vessel. As a non-invasive method, ultrasound does not involve radiation and sedation. Diagnosis of facial artery pseudoaneurysms is most commonly made with ultrasound, and Doppler ultrasound is essential. On grayscale imaging, facial artery pseudoaneurysms often appearanced of a fluid collection, Color Doppler imaging often show a well-defined swirl pattern named "yin and yang sign," the Spectral Doppler showed a diagnostic "to and fro" two-phase bidirectional arterial blood flow spectrum. It's particularly for the examination of facial artery pseudoaneurysms in children. Here, we report a case of facial foreign body abscess and facial artery pseudoaneurysm in a 19-month-old child 1 week after a sharpness injury that was diagnosed by ultrasound.
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Despite evidence suggesting the utility of Epstein-Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high-risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV-based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver-operator-characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross-validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV-based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93-0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0-92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9-3.0%) to 12.5% (9.9-15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255-290) to 50 (41-59). Combining the score with other risk factors (sex, first-degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5-year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high-risk population. Adding nonviral risk factors did not improve NPC prediction.